Unit 4a – Almost done!

Chapter 15: Microbial Mechanisms of Pathogenicity

• How microbes cause disease (figure 15.9)

Remember?

• Pathogenicity: The ability to cause disease.

• Virulence: The extent of pathogenicity.

• Most pathogenshave a preferredportal of entry

• Salmonella typhiswallowed vs. rubbed

• Strep pneumoniainhaled vs. swallowed

Numbers of Invading Microbes• _____: Infectious dose for 50% of a sample population.• _____: Lethal dose (toxin) for 50% of a sample population. • actual number depends on:

– virulence of pathogen– strength of host defenses

• for same pathogen and same person, infective dosage varies from day to day with strength of body defenses

Clickers…• What is the LD50 for the bacterial toxin tested in the

experiment below?

• Dilution # of animals # of animals mg/kg that died that survived

a. 6 0 6b. 12.5 0 6c. 25 3 3d. 50 4 2e. 100 6 0

Adherence factors

• for attachment to host cells

attachment by capsule

• Remember Unit 1 discussion of Biofilms?

attachment by filaments

attachment by hook

attachment by viral spikes

Virulence factors: how pathogens cause disease

• Many pathogens have multiple virulence factors

• Virulence factors have 5 general effects– adherence to host cells– entering into host cells– destruction of host cells– avoiding phagocytosis– evading immune responses

Good Essay Question!

Some exoenzymes of virulence• 1. collagenase: dissolves collagen (protein fibers in

connective tissue); softens up a tissue so infection can spread– Clostridium’s spread of gas gangrene

• 2. IgA proteases– Destroy our IgA antibodies– Gonorrhoea and meningococcal meningitis can do

• 3. hyaluronidase: dissolves hyaluronic acid (glue-like substance that holds cells together); helps infection to spread– Streptococcus sp.

hyaluronidase dissolving hyaluronic acid

• 4. lecithinase: dissolves cell membranes; pathogen can digest cell contents

enzymes of virulence

• 5. coagulases: clot blood; fibrin fibers coat pathogen, prevent phagocytosis– Staph (to wall off boils)

• 6. leukocidins: kill white blood cells– Staph aureus

• 7. kinases: dissolve clots (e.g. streptokinase)• 8. hemolysins: cause hemolysis (lysis of red

blood cells) – test for hemolysis on blood agar

– alpha hemolysis: partial hemolysis, causes greenish zone around colony on blood agar

– beta hemolysis: complete hemolysis, causes clear, colorless zone around colony

– gamma hemolysis: NO hemolysis

Other virulence factors

• _________: prevents phagocytosis, helps pathogen attach to host cell

Toxins

• Toxin: Substances that contribute to pathogenicity.• Toxigenicity: Ability to produce a toxin.• Toxemia: Presence of toxin in the host's blood.• Antitoxin: Antibodies our body produces against a

specific toxin. • Toxoid: Inactivated toxin used in a vaccine.

– When toxoids are injected as a vaccine, they stimulate antitoxin production so that immunity is produced

• Diphtheria and tetanus toxoid vaccination

Exotoxins

• Fig. 15.4

Endotoxins: Fig. 15.4

Endotoxins and the pyrogenic responsefigure 15.6

Sepsis and Septic Shock: pp. 639-641 (10th ed)

• Although blood is normally sterile, if the defenses of the cardiovascular and lymphatic systems fail, microbes could enter blood/lymph

• Septicemia: proliferation of pathogens in the blood– Fever– Sometimes causes organ damage

• Sepsis: systemic inflammatory response syndrome (SIRS)– Mediators of inflammation into the blood stream– Fever– rapid heart or respiratory rates– High count of white blood cells– Lymphangitis:

inflamed lymph vessels

Fig. 23.2 Relationship between the cardiovascular and lymphatic systems

Sepsis and Septic Shock continued• life-threatening systemic response to a bacterial infection

• First stage is sepsis– Fever, chills and accelerated breathing & heart rate

• Overwhelming infection leads to low blood pressure and low blood flow.– Shock

• Vital organs, such as the brain, heart, kidneys, and liver may not function properly or may fail. Decreased urine output from kidney failure may be one symptom.– Severe sepsis to septic shock

• Types– Gram-Negative Sepsis

• Endotoxic shock• 750,000 cases/ yr in US; at least 225,000 are fatal (textbook pg.

640)

– Gram-Positive Sepsis• Staph, Strep & Enterococcus

– Puerperal Sepsis• Childbirth fever• Nosocomial infection• Strep. pyogenes most frequent cause

• high risk patients:– Burns– Age >60 or the very young– post-surgery (especially intestinal)– abdominal trauma– advanced cancer– diabetes

septic shock

• mechanism: pathogens release endotoxins, exotoxins:

• these products stimulate release of chemicals from various host cells that produce the symptoms:– low blood pressure, especially when standing– rapid, weak pulse– fever (hypothermia in burn patients)– Low urine output– Agitation, confusion

septic shock• symptoms:

– sudden high fever– disorientation, confusion, irritability, somnolence– edema (swelling): face, hands, feet– dyspnea

• edema may constrict pharynx • bronchioles contract• death by asphyxiation may result

– circulatory stagnation• inadequate blood volume causes low blood

pressure, rapid weak pulse, possible total stagnation of bloodflow

septic shock

• treatment (not necessarily in this order)– inject epinephrine– open airway (intubation or tracheostomy)– oxygen if needed– restore blood volume: rapid IV – draw blood for blood gases and to culture

pathogen– broad spectrum drug (until pathogen is known)– monoclonal antibodies against endotoxin

Back to figure 15.9

In summary: Damage to host cells

• 1. By using the host’s nutrients – Siderophores: proteins pathogens produce to

get the iron they need from the host• 2. By causing direct damage in the

immediate vicinity of the invasion• 3. By producing toxins

Portals of ExitRespiratory tractCoughing and sneezingGastrointestinal tractFeces and salivaGenitourinary tractUrine and vaginal secretionsSkinBloodBiting arthropods and needles

or syringes